Nucleolin enhances the proliferation and migration of heat-denatured human dermal fibroblasts

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.

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Wound Healing Potential of Spirulina Protein on CCD-986sk Cells

Marine Drugs ◽

10.3390/md17020130 ◽

2019 ◽

Vol 17 (2) ◽

pp. 130

Author(s):

Ping Liu ◽

Jeong-Wook Choi ◽

Min-Kyeong Lee ◽

Youn-Hee Choi ◽

Taek-Jeong Nam

Keyword(s):

Wound Healing ◽

Dermal Fibroblast ◽

Fibroblast Cell ◽

Underlying Mechanism ◽

Human Dermal Fibroblast ◽

Dermal Fibroblasts ◽

Cyclin Dependent Kinase ◽

Pi3k Inhibitor Ly294002 ◽

And Migration ◽

Proliferation And Migration

Wound healing is a dynamic and complex process. The proliferation and migration of dermal fibroblasts are crucial for wound healing. Recent studies have indicated that the extracts from Spirulina platensis have a positive potential for wound healing. However, its underlying mechanism is not fully understood. Our previous study showed that spirulina crude protein (SPCP) promoted the viability of human dermal fibroblast cell line (CCD-986sk cells). In this study, we further investigated the wound healing effect and corresponding mechanisms of SPCP on CCD-986sk cells. Bromodeoxyuridine (BrdU) assay showed that SPCP promoted the proliferation of CCD-986sk cells. The wound healing assay showed that SPCP promoted the migration of CCD-986sk cells. Furthermore, cell cycle analysis demonstrated that SPCP promoted CCD-986sk cells to enter S and G2/M phases from G0/G1 phase. Western blot results showed that SPCP significantly upregulated the expression of cyclin D1, cyclin E, cyclin-dependent kinase 2 (Cdk2), cyclin-dependent kinase 4 (Cdk4), and cyclin-dependent kinase 6 (Cdk6), as well as inhibited the expression of CDK inhibitors p21 and p27 in CCD-986sk cells. In the meanwhile, SPCP promoted the phosphorylation and activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt). However, the phosphorylation of Akt was significantly blocked by PI3K inhibitor (LY294002), which in turn reduced the SPCP-induced proliferation and migration of CCD-986sk cells. Therefore, the results presenting in this study suggested that SPCP can promote the proliferation and migration of CCD-986sk cells; the PI3K/Akt signaling pathway play a positive and important role in these processes.

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Co-culture with human fetal epidermal keratinocytes promotes proliferation and migration of human fetal and adult dermal fibroblasts

Molecular Medicine Reports ◽

10.3892/mmr.2014.2798 ◽

2014 ◽

Vol 11 (2) ◽

pp. 1105-1110 ◽

Cited By ~ 8

Author(s):

ZHE WANG ◽

XIAOYU LIU ◽

DIANBAO ZHANG ◽

XILIANG WANG ◽

FENG ZHAO ◽

...

Keyword(s):

Dermal Fibroblasts ◽

Epidermal Keratinocytes ◽

And Migration ◽

Proliferation And Migration

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cRel expression regulates distinct transcriptional and functional profiles driving fibroblast matrix production in systemic sclerosis

Rheumatology ◽

10.1093/rheumatology/keaa272 ◽

2020 ◽

Vol 59 (12) ◽

pp. 3939-3951 ◽

Cited By ~ 1

Author(s):

Julie C Worrell ◽

Jack Leslie ◽

Graham R Smith ◽

Marco Y W Zaki ◽

Hannah L Paish ◽

...

Keyword(s):

Normal Skin ◽

Gene Signature ◽

Dermal Fibroblasts ◽

Skin Fibrosis ◽

Human Dermal Fibroblasts ◽

Murine Lung ◽

Skin Physiology ◽

Matrix Production ◽

And Migration ◽

Functional Profiles

Abstract Objectives NF-κB regulates genes that control inflammation, cell proliferation, differentiation and survival. Dysregulated NF-κB signalling alters normal skin physiology and deletion of cRel limits bleomycin-induced skin fibrosis. This study investigates the role of cRel in modulating fibroblast phenotype in the context of SSc. Methods Fibrosis was assessed histologically in mice challenged with bleomycin to induce lung or skin fibrosis. RNA sequencing and pathway analysis was performed on wild type and Rel−/− murine lung and dermal fibroblasts. Functional assays examined fibroblast proliferation, migration and matrix production. cRel overexpression was investigated in human dermal fibroblasts. cRel immunostaining was performed on lung and skin tissue sections from SSc patients and non-fibrotic controls. Results cRel expression was elevated in murine lung and skin fibrosis models. Rel−/− mice were protected from developing pulmonary fibrosis. Soluble collagen production was significantly decreased in fibroblasts lacking cRel while proliferation and migration of these cells was significantly increased. cRel regulates genes involved in extracellular structure and matrix organization. Positive cRel staining was observed in fibroblasts in human SSc skin and lung tissue. Overexpression of constitutively active cRel in human dermal fibroblasts increased expression of matrix genes. An NF-κB gene signature was identified in diffuse SSc skin and nuclear cRel expression was elevated in SSc skin fibroblasts. Conclusion cRel regulates a pro-fibrogenic transcriptional programme in fibroblasts that may contribute to disease pathology. Targeting cRel signalling in fibroblasts of SSc patients could provide a novel therapeutic avenue to limit scar formation in this disease.

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Promotive effects of human induced pluripotent stem cell-conditioned medium on the proliferation and migration of dermal fibroblasts

Biotechnology and Bioprocess Engineering ◽

10.1007/s12257-017-0221-1 ◽

2017 ◽

Vol 22 (5) ◽

pp. 561-568 ◽

Cited By ~ 9

Author(s):

Myeongsik Oh ◽

Yu Jin Kim ◽

Young Ju Son ◽

Hyuk Sang Yoo ◽

Ju Hyun Park

Keyword(s):

Stem Cell ◽

Conditioned Medium ◽

Pluripotent Stem Cell ◽

Induced Pluripotent Stem Cell ◽

Dermal Fibroblasts ◽

And Migration ◽

Induced Pluripotent ◽

Cell Conditioned Medium ◽

Proliferation And Migration

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A Novel Substance P-Based Hydrogel for Increased Wound Healing Efficiency

Molecules ◽

10.3390/molecules23092215 ◽

2018 ◽

Vol 23 (9) ◽

pp. 2215 ◽

Cited By ~ 4

Author(s):

Da Kim ◽

Ji Jang ◽

Song Jang ◽

Jungsun Lee

Keyword(s):

Wound Healing ◽

Substance P ◽

Dermal Fibroblasts ◽

Epidermal Keratinocytes ◽

Human Epidermal Keratinocytes ◽

In Vivo Experiments ◽

And Migration ◽

Proliferation And Migration

The neuropeptide substance P (SP) is known to stimulate wound healing by regulating the production of relevant cytokines as well as cell proliferation and migration. However, the therapeutic application of SP is limited by its low stability under biological conditions and oxidation during purification, formulation, and storage. To address this problem, we developed a novel formulation of SP as an SP gel, and investigated its wound healing activity both in vitro and in vivo. SP in SP gel was stable at various temperatures for up to 4 weeks. In vitro, SP gel exhibited more potential as a candidate wound-healing agent than SP alone, as evidenced by the observed increases in the proliferation and migration of human epidermal keratinocytes and human dermal fibroblasts. In vivo experiments showed that SP gel treatment enhanced the healing of full-thickness wounds in mice as compared to SP alone. These results demonstrate the benefits of SP gel as a promising topical agent for wound treatment.

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